Millions of Americans now entering midlife and old age were exposed to high levels of lead, a neurotoxin, as children. Evidence from animal and observational studies suggest that children exposed to lead may be at elevated risk for dementia in old age. More evidence is needed to characterize the nature of this risk. Such information would inform future research on disease prevention and assist communities in preparing for high disease burdens following lead-exposure events. The two studies proposed in this application will increase the evidence base on the long-term neurological consequences of childhood lead exposure using neuroimaging, genetic analysis, and advanced longitudinal statistical techniques. These studies will also help prepare the applicant for a successful interdisciplinary career integrating the fields of environmental health, cognitive aging, and observational epidemiology. The applicant's long-term career goal is to become a clinical neuropsychologist and independent academic researcher who conducts public health-oriented research on the degenerative consequences of environmental exposures. The proposed project integrates training and research plans to develop the applicant's expertise in these areas, with fellowship funds allowing for mentored training in (1) the application of neuroimaging to environmental health research, (2) the assessment of cognitive health and environmental exposures, (3) the application of quantitative analysis to longitudinal and behavioral genetic studies, and (4) the ethical conduct of research in observational studies. The training plan includes coursework and workshops, one-on-one mentorship, and participation in seminars and conferences. While ambitious, the planned studies and training plan are feasible because they will utilize existing data gathered in a population-representative longitudinal birth cohort, the Dunedin Study, which lead-tested 565 Study members in childhood (56% of living cohort) who are now in late midlife. This sub-cohort offers a globally unique opportunity to evaluate the long-term consequences of childhood lead exposure because, unlike with most lead-tested cohorts around the world, lead exposure was shared equally across socioeconomic groups in the Dunedin cohort. Study 1 will involve secondary analysis of existing neuroimaging data to determine whether childhood lead exposure relates to degenerative alterations in neural structure (Aim 1) or function (Aim 2) by late midlife. Study 2 will involve secondary analysis of existing genetic data to determine whether neurocognitive sequelae of childhood lead exposure are moderated by polymorphisms in genes suspected to alter the toxicodynamics of lead (Aim 3). These projects will build the evidence base on the neurodegenerative risk facing the millions of Americans who were exposed to lead in childhood, informing future research on disease prevention and future policy on community lead-exposure response. The fellowship will give the applicant unique, dual expertise in environmental health and degenerative disease epidemiology, and prepare him for future training focused on the application of epidemiological findings to disease prevention.